Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. We found that crosslinked enzyme crystals (CLECs) show stability under low pH, on storage and against proteolysis. These properties make them ideal for gut lumenal therapy. The patient would swallow a tablet or liquid suspension of CLEC particles composed of a needed metabolic enzyme or protein. The CLEC agent would survive the harsh acidic pH and proteolytic environment of the stomach, and pass into the proximal small intestine. The CLEC particle would then carry out its therapeutic biochemistry within the gut lumen while remaining resistant to degradation by endogenous proteases. In this Phase I study, we propose to develop two types of CLECs: Oxalyl-CoA decarboxylase for oral lumenal therapy and Oxalate oxidase to be used in the extracorporeal device/dialysis equipment. The Oxalyl-CoA decarboxylase-CLEC will perform its action in the duodenum while remaining as crystalline material or by release of activity by dissolution of the CLEC particle. This target was chosen to address the problems of current therapies of hyperoxaluna caused by excessive absorption of oxalate due to the absence of Oxalobacter formigenes bacterium in the intestine or due to inflammatory bowel disease. In addition, Oxalate oxidase-CLEC may be used in dialysis equipment or extracorprealdevices to reduce the oxalate content of blood in patients with Primary Hyperoxaluria. If successful, these approaches will lead to the introduction of novel, efficient enzyme therapy for the prevention of Oxalate Kidney Stones. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE